The overall aim of this proposal is to support the continuing development of the applicant as a research clinician and independent scientist in the field of drug abuse treatment. Two themes drive the applicant's work: 1) pharmacotherapies need to be developed that consider the heterogeneity of drug addicted samples and target specific subgroups, and 2) a better understanding of the biological and behavioral antecedents that contribute to drug abuse among certain vulnerable populations warrant investigation. Most medication development efforts to date have approached drug dependence as a unitary syndrome and have tested treatments in unselected samples. Many drug dependent individuals remain refractory or only partially responsive to this approach. Further, even among treatments with proven efficacy (e.g., methadone), certain subpopulations may do less well with these interventions and would benefit from a targeted intervention. During the proposed K02, the applicant will continue an ongoing line of inquiry by directing two studies to determine whether the identification and treatment of adult ADHD improves drug use outcome and psychopathology in opiate (DA-11444) and cocaine dependent (DA-11755) samples. Extending this approach to other comorbid disorders, the applicant will collaborate with junior investigators who are targeting ppharmacotherapies to nicotine- dependent schizophrenic patients, and marijuana and cocaine abusing individuals with schizophrenic and schizoaffective illness. Working with experienced investigators, the applicant plans to 1) use SPECT imaging to assess the neurobiologic dysfunction associated with ADHD and/or cocain abuse, and 2) better understand the sensitivity that vulnerable populations of women may have to alcohol and anxiolytic medications. Finally, the applicant will continue to contribute to a variety of educational activities and collaborate with young clinical investigators within the Division on Substance Abuse at Columbia University.